This is a competitive renewal application from an inter-institutional group of investigators with long-standing interest in Angelman syndrome (AS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS) to continue a Rare Diseases Clinical Research Center (RDCRC) within the Rare Diseases Clinical Research Network (RDCRN). The Center will focus on these three disorders based on the expectation that the near-term potential for meaningful therapy is strong. The specific aims for AS are 1) to conduct longitudinal assessments on individuals with AS according to genotype and 2) establish genotype-phenotype correlations based on molecular defect type. An exploratory aim is to examine the efficacy of existing therapies including developmental interventions with respect to the genotype-phenotype. Recent results from studies in animal models provide a basis for clinical trials in the next 5 years. The AS RDCRC sites will be located at Rady Children's Hospital San Diego, Baylor College of Medicine, Children's Hospital Boston, Greenwood Genetic Center, and Vanderbilt University;sites at Boston, Houston, and Nashville will utilize GCRCs. The Center is expected to function synergistically with the Intellectual and Developmental Disability Center-IDDRC (formerly the MRRC) at UAB, Baylor, Children's Hospital Boston, and Vanderbilt. An extensive training program is proposed for stimulating the entry of new investigators into clinical research on rare diseases (funded by 1RSF and PWSA). The Center will have active affiliation with and receive support from the Angelman Syndrome Foundation (ASF). A website for this RDCRC is available at www.circ.uab.edu. This site will be amplified to include a wide range of information for AS, RTT, and PWS.